RIBOSOMAL-PROTEIN S6 KINASE AND PROTEIN-KINASE-C ACTIVATION BY EPIDERMAL GROWTH-FACTOR AFTER TEMPORARY RENAL ISCHEMIA

An initial event in cell response to growth factors is the change in the state of phosphorylation of a number of cellular proteins playing a role in cell proliferation. The effects of a single dose of exogenously administered epidermal growth factor (EGF) on renal serine/threonine protein kinases such as ribosomal protein S6 kinase(s) and protein kinase C (PKC) and on [H-3]thymidine incorporation into tubule cell nuclei have been studied during the regenerative repair response after temporary renal ischemia in the rat, followed by reperfusion for up to 72 h. During the postischemic reflow, the PKC and S6 kinase activities increased at 24 and 72 h, respectively. EGF anticipated both increases: the PKC at 4 and the S6 kinase(s) at 24 h. Associated with this EGF-induced rise of S6 kinase activity, a significant increase in renal tubule cell proliferation was observed. These studies suggest the presence of a growth factor-activated serine/threonine threonine phosphorylation cascade in the rat kidney participating in the regulation of cell growth during recovery from an ischemic insult.